Hydrogels have many applications in the fields of medicine and life sciences, particularly in tissue engineering and regenerative medicine (TERM). Tissue engineering involves the construction or reconstruction of animal (e.g. human) tissue using cells and other components found within tissue, such as extracellular matrix components. A goal of TERM is to develop transplantable tissue and organs to address issues associated with organ transplants, such as organ shortage and organ rejection. TERM can enable medical professionals to use a patient's own cells to create new tissue and organs for the patient.
Regenerative medicine is the clinical application of this TERM technology for the purpose of regenerating damaged organs or tissue and for conducting implants and transplants using engineered tissue or organs. A goal of regenerative medicine is to use a patient's own cells to create transplantable tissue and organs to address the issues of organ shortage and immune system rejection that occur when transplanting donated organs.
The field of tissue engineering also includes tumor engineering, the use of cancer cells to create tumors for testing and research purposes, as well as personalized medicine. These tumors are three-dimensional aggregates of cells which attempt to mimic the conditions that occur in cancer in humans and other animals. Such tumors can be used to test cancer drugs in vitro, and may allow for more accurate testing by better simulating the conditions under which tumours develop within animals (e.g. by simulating cell-cell and cell-matrix interactions and by providing an extracellular matrix).
Hydrogels are employed in tissue engineering and regenerative medicine, for example for the formation of three-dimensional biological scaffolds in vitro and in vivo, and in some cases ex vivo. Some applications require that the hydrogels be injectable, such as the use of 3D bioprinters and other injection devices to build the scaffolds, transplant organs, and the like. Further, such hydrogels typically are also expected to provide a certain degree of mechanical strength and stiffness to support cell growth.
The conflicting requirements of injectability (preferably without damaging cells or other materials suspended within the hydrogel) and mechanical strength can render the design of such hydrogels difficult. Physical cross-linking, for example, may be employed to provide some mechanical strength while still allowing the hydrogel to be injected. For example, PCT patent publication no. WO 2014028209 A1 describes a hydrogel with a guest-host cross-linking mechanism, which softens or liquefies under pressure (i.e. undergoes shear-thinning) to allow injection. PCT patent publication no. WO 2011084710 A1 discusses another type of cross-linking, based on metal-ligand complexes.
However, physical cross-linking may not have sufficient mechanical strength to provide a suitable extracellular matrix for the generation of simulated tumours and other structures.